This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Background: Improvements in medical care and evacuation strategies on the field of combat have led to an increased number of veterans surviving disastrous war related injuries. While the improved survival rate is a medical advance, many veterans are returning from combat with amputations that require complex follow-up care, extensive rehabilitation, and expensive prosthetic services. Osseointegration is a surgical procedure that provides direct skeletal attachment between an implant and host tissue with proven success in dental, auricle, and transfemoral implants. However, one challenge with using natural biological fixation is attaining a strong skeletal interlock at the implant interface, a prerequisite for long-term implant function. Therefore, the objective of this study is to build upon the previous, clinical success of electrically induced bone growth used to augment fracture healing, and to expand this technology to improve osseointegration for amputees. Rationale: To validate the general hypothesis that electrical stimulation will increase skeletal attachment, a two-phase project has been designed that utilizes in vitro, in vivo, and in silico modalities to confirm the safety and efficacy of this technology prior to implementation in veteran and warrior amputees. The specific hypotheses for this model are founded on histological assessment, mechanical testing, and finite element analysis. Specifically, finite element-based simulation analysis of veteran and warrior amputee residual limbs imaged with computed tomography scans reveal that safe and effective densities and electric fields will be attainable at the bone-implant interface. Questions: While progress on this DBP has already been substantial, there are many additional hurdles that the Center will need to address in the future. Specific examples of these challenges include image-based modeling, uncertainty visualization, detailed simulation, and estimation accuracy. Design &Methods: The main goal of the Center collaboration with this DBP is to develop a comprehensive and validated computational infrastructure that will support the creation of patient specific models of the residual limbs of amputees to assist in the evaluation and treatment by means of osseointegration. This DBP is another example of the image-based modeling and simulation pipeline that serves as a central framework of the Center's research an development.